Benzonitrile, 4-bromo- → HCID 22503615, compound

HRID 1814580Notes

Reaction equation

HRID 1814580 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:6]([CH3:11])=[CH:7][CH:8]=[CH:9][CH:10]=1)=O.[Br:12][C:13]1[CH:20]=[CH:19][C:16](C#N)=[CH:15][CH:14]=1.P(Cl)(Cl)(Cl)=O.[CH2:26]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[CH3:27]>>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([C:1]2[N:2]=[C:3]([N:31]3[CH2:32][CH2:33][N:28]([CH2:26][CH3:27])[CH2:29][CH2:30]3)[C:5]3[C:6]([CH:11]=2)=[CH:7][CH:8]=[CH:9][CH:10]=3)=[CH:19][CH:20]=1

Participants

5

Reactant 4

HCID 12162Benzonitrile, 4-bromo-HCID 24813Phosphorus oxychlorideHCID 75111N-methyl-2-toluamideHCID 791961-Ethylpiperazine

Product 1

HCID 22503615HCID 22503615, compound

Conditions

Temperature
100 °C

Procedure

To 3-(4-bromophenyl)isoquinolin-1-one (3.86 g) obtained by reacting N-methyl-o-toluamide (7.50 g) and 4-bromobenzonitrile (9.10 g) according to the method of Example 10-1 was added phosphorus oxychloride (38.6 g), and the resulting mixture was heated at 100° C. for 2 hr. The reaction solution was evaporated, and to the resulting residue were added ethyl acetate and purified water. The ethyl acetate layer was washed with water, an aqueous solution of saturated sodium bicarbonate and brine, and dried over magnesium sulfate. The solvent was evaporated, and the resulting 1-chloro-3-(4-bromophenyl)isoquinoline was reacted as it was with N-ethylpiperazine (30 ml) at 120° C. for 8 hr. The reaction solution was evaporated, and to the resulting residue were added ethyl acetate and purified water. The ethyl acetate layer was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system), to give 3-(4-bromophenyl)-1-(4-ethylpiperazin-1-yl)isoquinoline (1.62 g) as a pale yellow oil.

Workup

  1. customThe reaction solution was evaporated
  2. additionto the resulting residue were added ethyl acetate
  3. custompurified water
  4. washThe ethyl acetate layer was washed with water
  5. dry with materialan aqueous solution of saturated sodium bicarbonate and brine, and dried over magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe resulting 1-chloro-3-(4-bromophenyl)isoquinoline was reacted as it
  8. customThe reaction solution was evaporated
  9. additionto the resulting residue were added ethyl acetate
  10. custompurified water
  11. washThe ethyl acetate layer was washed with water and brine
  12. dry with materialdried over magnesium sulfate
  13. customThe solvent was evaporated
  14. customthe resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system)

Sources & evidence

ORD record
ord-cfb74d4be30a4cb4b4114304dce47e4b
Source dataset
uspto-grants-2005_04
Patent number
US06875761B2

Reaction notes

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